Recording brain responses to TMS of primary motor cortex by EEG – utility of an optimized sham procedure

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  • Pedro C. Gordon
  • D. Blair Jovellar
  • Yu Fei Song
  • Christoph Zrenner
  • Paolo Belardinelli
  • Siebner, Hartwig Roman
  • Ulf Ziemann

Introduction: Electroencephalography (EEG) is increasingly used to investigate brain responses to transcranial magnetic stimulation (TMS). A relevant issue is that TMS is associated with considerable auditory and somatosensory stimulation, causing peripherally evoked potentials (PEPs) in the EEG, which contaminate the direct cortical responses to TMS (TEPs). All previous attempts to control for PEPs suffer from significant limitations. Objective/Hypothesis: To design an optimized sham procedure to control all sensory input generated by subthreshold real TMS targeting the hand area of the primary motor cortex (M1), enabling reliable separation of TEPs from PEPs. Methods: In 23 healthy (16 female) subjects, we recorded EEG activity evoked by an optimized sham TMS condition which masks and matches auditory and somatosensory co-stimulation during the real TMS condition: auditory control was achieved by noise masking and by using a second TMS coil that was placed on top of the real TMS coil and produced a calibrated sound pressure level. Somatosensory control was obtained by electric stimulation (ES) of the scalp with intensities sufficient to saturate somatosensory input. ES was applied in both the sham and real TMS conditions. Perception of auditory and somatosensory inputs in the sham and real TMS conditions were compared by psychophysical testing. Transcranially evoked EEG signal changes were identified by subtraction of EEG activity in the sham condition from EEG activity in the real TMS condition. Results: Perception of auditory and somatosensory inputs in the sham vs. real TMS conditions was comparable. Both sham and real TMS evoked a series of similar EEG signal deflections and induced broadband power increase in oscillatory activity. Notably, the present procedure revealed EEG potentials and a transient increase in beta band power at the site of stimulation that were only present in the real TMS condition. Discussion: The results validate the effectiveness of our optimized sham approach. Despite the presence of typical responses attributable to sensory input, the procedure provided evidence for direct cortical activation by subthreshold TMS of M1. The findings are relevant for future TMS-EEG experiments that aim at measuring regional brain target engagement controlled by an optimized sham procedure.

OriginalsprogEngelsk
Artikelnummer118708
TidsskriftNeuroImage
Vol/bind245
ISSN1053-8119
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
P.C.G. and C.Z. report funding through the EXIST translational research program from the German Federal Ministry for Economic Affairs and Energy. H.S. received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark. U.Z. received grants from the German Ministry of Education and Research (BMBF), European Research Council (ERC), German Research Foundation (DFG), Janssen Pharmaceuticals NV and Takeda Pharmaceutical Company Ltd., and consulting fees from Bayer Vital GmbH, Pfizer GmbH and CorTec GmbH, all not related to this work. The other authors declare no further competing financial interests.

Funding Information:
C.Z. acknowledges support from the Clinician Scientist Program at the Faculty of Medicine at the University of Tübingen [grant number 391–0-0]. The project has received funding from the European Research Council (ERC Synergy) under the European Union's Horizon 2020 research and innovation program (ConnectToBrain) [grant number 810377], and from an EXIST Transfer of Research grant by the German Federal Ministry for Economic Affairs and Energy [grant number 03EFJBW169]. H.S. holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the [grant number R186–2015–2138].

Publisher Copyright:
© 2021 The Author(s)

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